Project Summary: Vaccinating pregnant women to protect infants is a growing public health trend because this approach utilizes one vaccine to protect two people. However, it is unknown whether influenza vaccination during pregnancy protects infants against severe influenza or modifies the effectiveness of influenza vaccines subsequently administered to infants. It is critical that we understand the benefits and possible unintended consequences of this practice. Although influenza vaccines have been recommended for pregnant women for decades, vaccine uptake in this population remains low for reasons that are incompletely understood. The specific aims of this proposal are: 1) To determine whether maternal influenza vaccination during pregnancy protects infants 0 ? 12 months against influenza (defined as a) severe influenza (i.e., hospitalization), b) laboratory-confirmed influenza or c) any influenza or influenza-like illness), and whether the effect varies by trimester of vaccination; 2) Evaluate whether the effectiveness of Infants' first influenza vaccination at age 6 ? 12 months is modified by influenza vaccination during pregnancy; and 3) Examine whether influenza non-vaccination during pregnancy clusters geographically, and determine if those clusters are associated with influenza and influenza-like illnesses during pregnancy. The aims will leverage advanced didactic training, benefit from an experienced mentorship team, and apply use of cutting-edge causal inference and geographical cluster analysis techniques. They will harness the incredible depth and breadth of the Kaiser Permanente Northern California's population data and the comprehensive training environment afforded by Kaiser Permanente Division of Research. The direct impact of this research is that it can lead to changes to current policies regarding influenza vaccination in pregnant women. The career development component of the application is designed to provide Dr. Zerbo with expertise in vaccinology, advance statistical methods and additional research skills with the goal to prepare him to become an independent investigator in vaccine effectiveness focused on pregnant women and infants. As more vaccines are developed for pregnant women, determining their effectiveness and their interaction and effect on infant immune system will be increasingly important.